Isabelle Bartram, Nicola Gökbuget, Cornelia Schlee, Sandra Heesch, Lars Fransecky, Stefan Schwartz, Reingard Stuhlmann, Kerstin Schäfer-Eckhart, Michael Starck, Albrecht Reichle, Dieter Hoelzer, Claudia Baldus, Martin Neumann
- Background: Risk stratification, detection of minimal residual disease (MRD), and implementation of novel therapeutic agents have improved outcome in acute lymphoblastic leukemia (ALL), but survival of adult patients with T-cell acute lymphoblastic leukemia (T-ALL) remains unsatisfactory. Thus, novel molecular insights and therapeutic approaches are urgently needed.
Methods: We studied the impact of B-cell CLL/lymphoma 11b (BCL11b), a key regulator in normal T-cell development, in T-ALL patients enrolled into the German Multicenter Acute Lymphoblastic Leukemia Study Group trials (GMALL; n = 169). The mutational status (exon 4) of BCL11b was analyzed by Sanger sequencing and mRNA expression levels were determined by quantitative real-time PCR. In addition gene expression profiles generated on the Human Genome U133 Plus 2.0 Array (affymetrix) were used to investigate BCL11b low and high expressing T-ALL patients.
Results: We demonstrate that BCL11b is aberrantly expressed in T-ALL and gene expression profiles reveal an association of low BCL11b expression with up-regulation of immature markers. T-ALL patients characterized by low BCL11b expression exhibit an adverse prognosis [5-year overall survival (OS): low 35% (n = 40) vs. high 53% (n = 129), P = 0.02]. Within the standard risk group of thymic T-ALL (n = 102), low BCL11b expression identified patients with an unexpected poor outcome compared to those with high expression (5-year OS: 20%, n = 18 versus 62%, n = 84, P < 0.01). In addition, sequencing of exon 4 revealed a high mutation rate (14%) of BCL11b.
Conclusions: In summary, our data of a large adult T-ALL patient cohort show that low BCL11b expression was associated with poor prognosis; particularly in the standard risk group of thymic T-ALL. These findings can be utilized for improved risk prediction in a significant proportion of adult T-ALL patients, which carry a high risk of standard therapy failure despite a favorable immunophenotype.
MetadatenAuthor: | Isabelle Bartram, Nicola GökbugetGND, Cornelia Schlee, Sandra Heesch, Lars Fransecky, Stefan SchwartzORCiDGND, Reingard Stuhlmann, Kerstin Schäfer-Eckhart, Michael Starck, Albrecht Reichle, Dieter HoelzerGND, Claudia BaldusORCiDGND, Martin Neumann |
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URN: | urn:nbn:de:hebis:30:3-347168 |
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DOI: | https://doi.org/10.1186/s13045-014-0051-y |
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ISSN: | 1756-8722 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/25023966 |
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Parent Title (English): | Journal of hematology & oncology |
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Publisher: | BioMed Central |
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Place of publication: | London |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2014/07/25 |
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Date of first Publication: | 2014/07/15 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2014/07/25 |
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Tag: | Adult T-cell acute lymphoblastic leukemia; BCL11b; Expression; Mutation; Outcome; Standard risk |
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Volume: | 7 |
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Issue: | 51 |
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Page Number: | 10 |
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First Page: | 1 |
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Last Page: | 10 |
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HeBIS-PPN: | 366011677 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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